Drug-membrane interactions

C. Immobilized artifidal membranes -screens for drug-membrane interactions. Adv. Drug Del. Revs. 1996, 23, 229-256. 

Lundahl, P., Beigi, F. Immobilized liposome chromatography of drugs for model analysis of drug-membrane interactions. Adv. Drug Deliv. Rev. 1997, 23, 221-227. 

A CRO may also allow for the in-house introduction of specialized lipophilic scales by transferring routine measurements. While the octanol-water scale is widely applied, it may be advantageous to utilize alternative scales for specific QSAR models. Solvent systems such as alkane or chloroform and biomimetic stationary phases on HPLC columns have both been advocated. Seydel [65] recently reviewed the suitabihty of various systems to describe partitioning into membranes. Through several examples, he concludes that drug-membrane interaction as it relates to transport, distribution and efficacy cannot be well characterized by partition coefficients in bulk solvents alone, including octanol. However, octanol-water partition coefficients will persist in valuable databases and decades of QSAR studies. 

R. P. New approaches to drug design and delivery based on drug-membrane interactions. Drug Des. Deliv. 1991, 7, 75-118. 

Dynamic aspects of drugs delivered into lipid bilayer membranes are significant in discussing bioactivities and the mechanism of the drug-membrane interactions. So far, however, the dynamic properties of drugs in the membrane interior have not been well understood. No systematic NMR experiments have been carried out because of the low concentration of the bilayer interior. In this section, we illustrate how to obtain dynamic features of drug molecules trapped in membranes by NMR. 

Seydel, J. K. Coats, E. A. Cordes, H. P. Weise, M., Drug membrane interactions and the importance for drug transport, distribution, accumulation, efficacy and resistance, Arch. Pharm. (Weinheim) 327, 601-610 (1994). 

D. A. Middleton, NMR methods for characterising ligand-receptor and drug-membrane interactions in pharmaceutical research. Annu. Rep. NMR Spectrosc., 2007, 60, 39-75. 

Bassolino-Klimas, D. Alper, H. E. Stouch, T. R., Drug-membrane interactions studied by molecular dynamics simulation size dependence of diffusion, Drug Des. Discov. 1996,13, 135-141. 

Platen, G.E., Skar, M., Luthman, K. and Brandi, M. (2007) Drug permeability across a phospholipid vesicle based barrier 3. Characterization of drug-membrane interactions and the, effect of agitation on the barrier integrity and on the permeability. European Journal of Pharmaceutical Sciences, 30, 324—332. 

M. A. Perillo (2002). The drug-membrane interaction its modulation at the supramolecular level. Recent Res. Dev. Biophys. Chem. 2 105-121. 

Drug-Membrane Interactions Analysis, Drug Distribution, Modeling. Joachim K. Seydel, Michael Wiese 1... 

Artificial membranes are used to study the influence of drug structure and of membrane composition on drug-membrane interactions. Artificial membranes that simulate mammalian membranes can easily be prepared because of the readiness of phospholipids to form lipid bilayers spontaneously. They have a strong tendency to self-associate in water. The macroscopic structure of dispersions of phospholipids depends on the type of lipids and on the water content. The structure and properties of self-assembled phospholipids in excess water have been described [74], and the mechanism of vesicle (synonym for liposome) formation has been reviewed [75]. While the individual components of membranes, proteins and lipids, are made up of atoms and covalent bonds, their association with each other to produce membrane structures is governed largely by hydrophobic effects. The hydrophobic effect is derived from the structure of water and the interaction of other components with the water structure. Because of their enormous hydrogen-bonding capacity, water molecules adopt a structure in both the liquid and solid state. 

Liposome preparations have been shown to be suitable not only for studying special drug-membrane interaction effects in vitro but also for use as drug carriers. Various techniques have been developed and described to prepare homogeneous unil-... 

Liposomal preparations are of interest for studying not only drug-membrane interactions but also membrane permeability and drug transport... 

Events which can arise from drug-membrane interaction are summarized below. 

The concept of accessory binding sites [28] may implicate the role of different hydrogen-bonding characteristics. Thus, the supplementary use of PGDP or other proton acceptor systems may lead to a better understanding of drug-membrane interaction. 

Analytical Tools for the Analysis and Quantification of Drug-Membrane Interactions... 

Studies of Drug-Membrane Interactions using Phospholipid Monolayers... 

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